RT Journal Article SR Electronic T1 The Bartonella autotransporter CFA is a protective antigen and hypervariable target of neutralizing antibodies blocking erythrocyte infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.29.462357 DO 10.1101/2021.09.29.462357 A1 Lena K. Siewert A1 Aleksandr Korotaev A1 Jaroslaw Sedzicki A1 Katja Fromm A1 Daniel D. Pinschewer A1 Christoph Dehio YR 2021 UL http://biorxiv.org/content/early/2021/09/29/2021.09.29.462357.abstract AB Antibodies are key to the clearance of Bartonella bacteremia, but the mechanisms and targets of protective antibodies are unknown and bacterial evasion strategies remain elusive. We studied experimental Bartonella taylorii infection of mice, its natural host, and investigated protective immune responses. Clearance of bacteremia depended on specific antibodies that interfere with bacterial attachment to erythrocytes. Accordingly, antibodies were effective in the absence of complement and Fc-receptors. Moreover, they formed independently of B-cell hypermutation and isotype class switch. The cloning of neutralizing monoclonal antibodies (mAbs) led to the identification of the bacterial autotransporter CFA as a protective antibody target, and vaccination against CFA protected against Bartonella bacteremia. MAb binding mapped to a region of CFA that is hypervariable in both human- and mouse-pathogenic Bartonella strains, suggesting mutational antibody evasion. These insights further our understanding of Bartonella immunity and immune evasion and elucidate mechanisms driving high Bartonella prevalence in the wild.Competing Interest StatementD. D. P is a founder, consultant and shareholder of Hookipa Pharma Inc. commercializing arenavirus-based vector technology, and he is listed as inventor on corresponding patents. The remainder authors declare no competing interests.